TY - JOUR
T1 - Human beta-defensin-3 promotes wound healing in infected diabetic wounds
AU - Hirsch, Tobias
AU - Spielmann, Malte
AU - Zuhaili, Baraa
AU - Fossum, Magdalena
AU - Metzig, Marie
AU - Koehler, Till
AU - Steinau, Hans Ulrich
AU - Yao, Feng
AU - Onderdonk, Andrew Bruce
AU - Steinstraesser, Lars
AU - Eriksson, Elof
PY - 2009
Y1 - 2009
N2 - Background: Infected wounds present a major complication in patients with diabetes. Staphylococcus aureus is the most common single isolate in diabetic wounds. Human beta-defensin (hBD)-3 is antimicrobial active and appears to play a key role in the immune response. The present study aimed to analyse the effect of hBD-3 expression in a model of infected diabetic wounds. Methods: Excisional wounds were created on the backs of Yorkshire pigs and Ad5-CMV-hBD-3 vectors were microseeded. Wounds were inoculated with S. aureus, covered with a polyurethane chamber and analysed for transgene expression, bacterial infection, re-epithelialization, wound contraction, wound fluid production and blood vessel formation. Results: hBD-3-treated wounds showed a total bacterial load of 2.1 × 108 colony-forming units (CFU)/g tissue, versus 1.3 × 109 CFU/g tissue for controls (p < 0.001) at day 4. At day 12, no statistical difference could be detected. Re-epithelialization showed 75 ± 15% wound closure for hBD-3 expressing wounds and 50 ± 16% for controls (p < 0.01). hBD-3 expression was in the range 15-20 ng/ml of wound fluid during day 1-4. The lower dose of 2 × 109 Ad5-CMV-hBD-3 showed no effect, suggesting a dose dependency for hBD-3. Conclusions: In the present study, we show that hBD-3 expression significantly promotes wound closure in S. aureus infected diabetic wounds in a preclinical large-animal model. Furthermore, a ten-fold reduction of bacterial growth on day 4 was detected. These findings indicate that beta-defensin-3 may play a major role in diabetic wound healing and wound infections.
AB - Background: Infected wounds present a major complication in patients with diabetes. Staphylococcus aureus is the most common single isolate in diabetic wounds. Human beta-defensin (hBD)-3 is antimicrobial active and appears to play a key role in the immune response. The present study aimed to analyse the effect of hBD-3 expression in a model of infected diabetic wounds. Methods: Excisional wounds were created on the backs of Yorkshire pigs and Ad5-CMV-hBD-3 vectors were microseeded. Wounds were inoculated with S. aureus, covered with a polyurethane chamber and analysed for transgene expression, bacterial infection, re-epithelialization, wound contraction, wound fluid production and blood vessel formation. Results: hBD-3-treated wounds showed a total bacterial load of 2.1 × 108 colony-forming units (CFU)/g tissue, versus 1.3 × 109 CFU/g tissue for controls (p < 0.001) at day 4. At day 12, no statistical difference could be detected. Re-epithelialization showed 75 ± 15% wound closure for hBD-3 expressing wounds and 50 ± 16% for controls (p < 0.01). hBD-3 expression was in the range 15-20 ng/ml of wound fluid during day 1-4. The lower dose of 2 × 109 Ad5-CMV-hBD-3 showed no effect, suggesting a dose dependency for hBD-3. Conclusions: In the present study, we show that hBD-3 expression significantly promotes wound closure in S. aureus infected diabetic wounds in a preclinical large-animal model. Furthermore, a ten-fold reduction of bacterial growth on day 4 was detected. These findings indicate that beta-defensin-3 may play a major role in diabetic wound healing and wound infections.
KW - Bacterial infection
KW - Gene transfer
KW - Host defense peptides
KW - Innate immunity
KW - S. aureus
KW - Wound healing
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U2 - 10.1002/jgm.1287
DO - 10.1002/jgm.1287
M3 - Article
C2 - 19115333
AN - SCOPUS:65349178179
SN - 1099-498X
VL - 11
SP - 220
EP - 228
JO - Journal of Gene Medicine
JF - Journal of Gene Medicine
IS - 3
ER -